The primary aims of the research proposal are: 1. The discovery in a collaborative manner between clinicians and biological scientists of metabolic disorders hitherto not described and associated with mental retardation, childhood psychoses and other neurological disorders; 2. To carry out basic investigations at the molecular level into the etiology and prevention of mental retardation; and 3. To provide an environment for the training of young scientists interested in problems of mental retardation. This program project contains six components. All the proposals arose from work done the first years of the current Program Project Grant HD-06576 (1973/78). The program unites biomedical scientists of diverse disciplines in a combined effort to search for an understanding of disorders leading to mental disorders and their treatment. All the research proposals are disease oriented, yet they are so designed as to answer also hitherto unsolved problems of human genetics. Project I aims at diagnosing, by the use of sophisticated analytical techniques, metabolic abnormalities associated with MR and childhood psychoses. Project II is a continuation of the study of abnormalities of carbohydrate metabolism in relation to brain funtion. Projects III, IV and V arising also out of previous investigations, seek an understanding of the molecular basis of three groups of enzyme deficiency diseases, metachromatic leukodystrophy, galactosemia and phenylketonuria. Project VI, in continuation of current researches, aims at defining in detail the relative contributions of glucose and ketone bodies, particularly of D(minus)- and L (plus)-beta-hydroxybutyrate as carbon sources for synthesis of CNS constituents during myelination.